Genistein-induced apoptosis of human breast cancer MCF-7 cells involves calpain-caspase and apoptosis signaling kinase 1-p38 mitogen-activated protein kinase activation cascades.
Anticancer Drugs
; 18(6): 649-57, 2007 Jul.
Article
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| MEDLINE
| ID: mdl-17762393
ABSTRACT
The molecular mechanisms of genistein-induced apoptosis of human breast cancer MCF-7 cells were investigated. Genistein showed 50% cell growth inhibition at IC50=27.5+/-0.8 micromol/l in 24 h incubation under 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay conditions. Genistein is known to express both cell growth activity at nanomolar concentrations and anti-cell growth activity at micromolar concentrations. It was found that genistein at 100 micromol/l concentration effectively induced apoptosis of MCF-7 cells in 24 h. Genistein-induced apoptosis involved activation of calpain, caspase 7 and poly(ADP ribose) polymerase. Dantrolene, an inhibitor of Ca release from the endoplasmic reticulum, inhibited genistein-induced activation of calpain and caspase 7, in addition to effectively negating genistein-induced apoptosis. MCF-7 cells treated with genistein also showed increased phosphorylation of p38 mitogen-activated protein kinase, whereas no effect was observed for extracellular signal-regulating kinase 1/2. Phosphorylation of apoptosis signaling kinase 1, an upstream regulator of p38 mitogen-activated protein kinase, was also increased by genistein treatment. Genistein-induced phosphorylation of apoptosis signaling kinase 1 and p38 mitogen-activated protein kinase was diminished by the presence of dantrolene. These results suggest that genistein-induced apoptosis in MCF-7 cells is mediated through calpain-caspase 7 and apoptosis signaling kinase 1-p38 mitogen-activated protein kinase activation cascades that involve Ca release from the endoplasmic reticulum.
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Banco de datos:
MEDLINE
Asunto principal:
Calpaína
/
Apoptosis
/
Genisteína
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MAP Quinasa Quinasa Quinasa 5
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Proteínas Quinasas p38 Activadas por Mitógenos
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Caspasa 7
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Antineoplásicos Fitogénicos
Límite:
Female
/
Humans
Idioma:
En
Año:
2007
Tipo del documento:
Article